Morphine
Morphine
Generic Name
Morphine
Mechanism
Morphine preferentially binds to μ‑opioid receptors (MOR) in the central nervous system (cerebral cortex, thalamus, brainstem) and peripheral pain pathways.
• G‑protein coupling inhibits adenylate cyclase → ↓cAMP, reduces calcium influx, and ↑potassium conductance → neuronal hyperpolarisation.
• Resulting in suppressed nociceptive neurotransmission, analgesia, sedation, and respiratory depression.
• Peripheral MOR activation produces constipation and decreased gastrointestinal motility.
*Key phrase: “morphine mechanism of action” is crucial for understanding opioid pharmacodynamics.*
Pharmacokinetics
- Absorption: Rapid oral bioavailability (~30–70 %); IV/IM/SC immediate and complete (100 %).
- Distribution: Extensive; high protein binding (~55 %); crosses the blood–brain barrier efficiently.
- Metabolism: Mainly glucuronidation in the liver to morphine‑3‑glucuronide (inactive) and morphine‑6‑glucuronide (M6G) (potently analgesic, 20–30 % of plasma exposure).
- Elimination: Renal excretion (~10–15 % unchanged; metabolites excreted renally).
- Half‑life: 3–4 hrs (IV), extends to 3–5 hrs with repeated dosing due to enzyme induction.
- Special populations: Reduced clearance in hepatic/renal impairment; higher activity of M6G in renal failure → risk of respiratory depression.
Indications
- Acute pain: post‑operative, traumatic, neuropathic episodes.
- Chronic cancer pain; adjunct to multimodal analgesia.
- Dyspnea in palliative patients.
- Septic & hemorrhagic shock: adjunct to norepinephrine for refractory hypotension.
- Anesthesia: intra‑operative analgesia (bolus) and post‑operative patient‑controlled analgesia.
- Hypertensive crisis (rare adjunct with α‑agonists).
Contraindications
- Absolute contraindications:
- Severe opioid dependence or addiction without taper plan.
- Acute, severe respiratory depression.
- Severe liver/renal disease without dose adjustment.
- Relative contraindications:
- Severe asthma, COPD, or COPD exacerbation.
- Obstructive uropathy or bowel obstruction (risk of obstruction).
- Pregnancy (Category C); avoid in breastfeeding unless benefits outweigh risks.
- Warnings:
- Pediatric dosing requires strict weight‑based calculation; avoid in <2 yr olds with immature pathways unless critically indicated.
- Geriatric patients: higher sensitivity to respiratory depression and orthostatic hypotension.
- Risk of tolerance, hyperalgesia, and opioid-induced hyperalgesia with chronic use.
Dosing
| Route | Initial Adult Dose | Titration | Notes |
| IV/SC/IM | 2–5 mg (IV/SC) or 5–10 mg (IM) every 4 hrs PRN | Increase 2 mg IV every 30–60 min until effect | Onset 1–3 min (IV). |
| Oral | 10–20 mg q6 hrs | 10 mg every 3 hrs | Monitor for constipation & tolerance. |
| Rectal | 10 mg every 4–6 hrs | Conservative titration | Avoid in ulcerative colitis. |
| Infusion (continuous IV) | 0.1–0.5 mg/kg/h | Adjust by pain score, vitals | Safer for major surgery & critical care. |
| Pediatric | 0.1–0.15 mg/kg IV/IM q4 hrs | Increase 0.01 mg/kg every 30 min | No routine use <2 yrs; ensure formulation purity. |
• Kill‑switch: if inadequate analgesia, consider morphine‑8‑Glucuronide or NSAID/Narcotic synergy; for hyperalgesia, switch to ketamine.
• Adjuncts: bowel regimen (senna/iberis + stool softener), anti‑emetics (ondansetron).
Adverse Effects
- Common:
- Nausea/vomiting
- Constipation (most frequent)
- Sedation, pruritus, dizziness
- Hypotension (especially in volume depleted patients)
- Serious:
- Respiratory depression → hypoxia, apnea, death
- Severe bradycardia from vagal tone (rare)
- Acute respiratory distress syndrome (in high doses)
- Severe allergic reactions (anaphylaxis, although rare)
- Opioid-induced hyperalgesia and tolerance
- Significant renal impairment leading to accumulation of M6G.
Monitoring
- Respiratory: rate, depth, SpO₂, arterial blood gases if unstable.
- Vitals: BP, HR, O₂ saturation; watch for orthostatic hypotension.
- Neurologic: level of consciousness, agitation, pain scores (VAS/NRS).
- Gastrointestinal: bowel movements, stool consistency, pain after meals.
- Laboratory: renal function (CrCl), liver enzymes if chronic therapy.
- Patient‑reported: opioid side‑effect checklist, breakthrough pain frequency.
Clinical Pearls
- Peptide metabolite dominance: M6G is the primary analgesic metabolite; in renal failure, its accumulation can precipitate severe respiratory depression—dose adjustment or use alternative agents is essential.
- Cumulative tolerance: Do not exceed 50 % increase in dose over 48 hrs; consider quality‑of‑life and opioid rotation when breakthrough pain persists.
- First‑dose choice: For patients with high risk of respiratory depression, start with the lowest feasible dose (e.g., 0.5 mg IV) and titrate slowly.
- Kidney ⟶ liver interaction: Morphine is safer than codeine in hepatic impairment because codeine relies on CYP2D6 for activation; morphine’s pathway is independent of CYP2D6.
- Pediatric nuances: Use a Poiseuille equation‑derived infusion rate calculator for continuous infusion; avoid repeated large boluses to mitigate postoperative nausea.
- Converter tables: Keep an up‑to‑date morphine‑equivalent dose chart for opioid rotation and step‑down strategies.
- Constipation prophylaxis: Initiate stool softener + mild laxative at mg/kg/day of morphine equivalents to avoid mucosal damage.
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